This invention relates to controlled release to a liquid medium of substances having an amino group; the invention also relates to compounds used in such release, and to precursors in the synthesis of such compounds.
There are numerous situations in which it is desirable to control the release of amino-group-containing substances to a liquid medium. By way of example, it may be desirable to control the release of an amino-group-containing drug or cytotoxin to a cell population or specific members of a cell population. It may also be desirable to control cleavage of various cross-linked proteins or peptides, for example, in analyzing the spatial relationships in a complex of large amino-group-containing molecules such as peptides or proteins. [The term "peptide" will be used in this application to include proteins, no matter how large, as well as shorter-chain peptides.]
One specific situation in which controlled release is desirable is delivering a biologically active compound through the cell membrane to inner cell structures, for example where the compound has a diminished effect if trapped in the medium outside the cell membrane but is more potent once released inside the cell.
It is also desirable to deliver biologically active compounds to selected cells in a heterogeneous cell population. For example, in treating diseased or infected cells such as virus-infected cells or transformed or malignant cells, it is desirable to deliver cytotoxins to the diseased or malignant cells but not to normal cells.
One approach disclosed for targeting biologically active compounds to malignant cells uses an antibody-toxin conjugate. The antibody is specific for malignant cells and delivers the toxin to them. To be effective, such systems should deliver the toxin with high selectivity to the target cells without unnecessarily reducing the effectiveness of the active substance. These problems are particularly important where the goal is destruction of infected or diseased cells in vivo without harming normal cells.
Some of these approaches require that the antibody-toxin conjugate retain the toxicity of the toxin component. Other approaches depend on disulfide bond cleavage, a phenomenon that may be difficult to control temporally and spatially to avoid release of the toxin before delivery to the targeted cells.